Dataset Information

Diabetic dyslipidemia and exercise alter the plasma low-density lipoproteome in Yucatan pigs.

ABSTRACT: Although low-density lipoprotein (LDL) plays a predominant role in atherogenesis, the low-density lipoproteome has not been fully characterized. Moreover, alterations from a Western diet, diabetes, and physical inactivity on this proteome have yet to be determined. Accordingly, relative quantification was determined in LDL proteins from male Yucatan diabetic dyslipidemic (DD) swine in the early stages of atherosclerosis compared to healthy control (C) and non-diabetic hyperlipidemic (H) swine. Importantly, coronary vascular dysfunction was prevented by aerobic exercise training in these animals (DDX) without altering total LDL concentration. Using 2-DE, Western blot, label-free quantitative MS, and selected reaction monitoring, alterations in the abundance of apolipoproteins A-I, B, C-III, D, E, and J and noncovalently associated proteins were determined in LDL isolated using fast protein liquid chromatography. At least 28 unique proteins, many of which were novel, were identified with high confidence. An apolipoprotein E isoform demonstrated stronger correlation to disease (percent of coronary artery segments with intimal thickening) than some traditional risk factors (total cholesterol, LDL cholesterol, and LDL/HDL cholesterol). Taken together, this work identifies new possible biomarkers, potential therapeutic targets for atherosclerosis, and generates new hypotheses regarding the role of LDL in atherogenesis.

SUBMITTER: Richardson MR

PROVIDER: S-EPMC2859442 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Diabetic dyslipidemia and exercise alter the plasma low-density lipoproteome in Yucatan pigs.

Richardson Matthew R MR Lai Xianyin X Dixon Joseph L JL Sturek Michael M Witzmann Frank A FA

Proteomics 20090501 9

Although low-density lipoprotein (LDL) plays a predominant role in atherogenesis, the low-density lipoproteome has not been fully characterized. Moreover, alterations from a Western diet, diabetes, and physical inactivity on this proteome have yet to be determined. Accordingly, relative quantification was determined in LDL proteins from male Yucatan diabetic dyslipidemic (DD) swine in the early stages of atherosclerosis compared to healthy control (C) and non-diabetic hyperlipidemic (H) swine. I ...[more]

PMID: 19402046

Similar Datasets

Project description:BackgroundAlthough total plasma lipoproteome consists of proteins that have shown promises as biomarkers that can identify Alzheimer's disease (AD), effect sizes are modest. The objective of this study is to provide initial proof-of-concept that the plasma lipoproteome more likely differ between AD cases and controls when measured in individual plasma lipoprotein fractions than when measured as total in immunodepleted plasma.MethodsWe first developed a targeted proteomics method based on selected reaction monitoring (SRM) and liquid chromatography and tandem mass spectrometry for measurement of 120 tryptic peptides from 79 proteins that are commonly present in plasma lipoproteins. Then in a proof-of concept case-control study of 5 AD cases and 5 sex- and age-matched controls, we applied the targeted proteomic method and performed relatively quantification of 120 tryptic peptides in plasma lipoprotein fractions (fractionated by sequential gradient ultracentrifugation) and in immunodepleted plasma (of albumin and IgG). Unadjusted p values from two-sample t-tests and overall fold change was used to evaluate a peptide relative difference between AD cases and controls, with lower p values (<?0.05) or greater fold differences (>?1.05 or?<?0.95) suggestive of greater peptide/protein differences.ResultsWithin-day and between-days technical precisions (mean %CV [SD] of all SRM transitions) of the targeted proteomic method were 3.95% (2.65) and 9.31% (5.59), respectively. Between-days technical precisions (mean % CV [SD]) of the entire plasma lipoproteomic workflow including plasma lipoprotein fractionation was 27.90% (14.61). Ten tryptic peptides that belonged to 5 proteins in plasma lipoproteins had unadjusted p values?<?0.05, compared to no peptides in immunodepleted plasma. Furthermore, 27, 32, 17, and 20 tryptic peptides in VLDL, IDL, LDL and HDL, demonstrated overall peptide fold differences?>?1.05 or?<?0.95, compared to only 6 tryptic peptides in immunodepleted plasma. The overall comparisons, therefore, suggested greater peptide/protein differences in plasma lipoproteome when measured in individual plasma lipoproteins than as total in immunodepleted plasma. Specifically, protein complement C3's peptide IHWESASLLR, had unadjusted p values of 0.00007, 0.00012, and 0.0006 and overall 1.25, 1.17, 1.14-fold changes in VLDL, IDL, and LDL, respectively. After positive False Discovery Rate (pFDR) adjustment, the complement C3 peptide IHWESASLLR in VLDL remained statistically different (adjusted p value?<?0.05).DiscussionThe findings may warrant future studies to investigate plasma lipoproteome when measured in individual plasma lipoprotein fractions for AD diagnosis.

Project description:BACKGROUND:It is important to achieve the low-density lipoprotein cholesterol (LDL-C) goal recommended by clinical guidelines in managing the risk of cardiovascular (CV) events, however, the current management of LDL-C in actual clinical settings is suboptimal. We examined the LDL-C level among patients with dyslipidemia against the 2015 Korean guidelines, the crude rates of CV events based on LDL-C goal achievement, and the factors associated with LDL-C goal achievement. METHODS:This was a retrospective cohort study using the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) database from 2006 to 2013. Patients who had a health examination with LDL-C measurement between January 1, 2007, and December 31, 2011 were identified. Patients were required to have at least one diagnosis of dyslipidemia during the 1 year before the index date, defined as the first date of LDL-C measurement. The 2015 Korean guidelines were used to measure LDL-C goal achievement based on the CV risk level. Crude CV event rates were calculated for total and individual CV events as the number of events divided by person-years (PYs) during the follow-up period. CV events included acute coronary syndrome, ischemic stroke, peripheral artery disease, CV death, and all-cause death. Factors associated with LDL-C goal achievement were assessed using logistic regression. RESULTS:In the NHIS-HEALS database, 69,942 patients met the eligibility criteria: 36.7%, 22.5%, 20.1%, and 20.6% were among the very high-, high-, moderate-, and low-risk groups for the CV events, respectively, as defined by the 2015 Korean guidelines. Approximately half of the patients with dyslipidemia (47.6%) achieved their recommended LDL-C goal, but the achievement rates were substantially different across CV risk levels (17.6%, 47.2%, 66.9%, and 82.4% for very high-, high-, moderate-, and low-risk groups, respectively; P<0.0001). The crude event rate of total CV events during the follow-up period in the LDL-C goal non-achievers was higher than that in the LDL-C goal achievers (24.35/100 PYs vs. 11.93/100 PYs; P<0.0001). LDL-C goal achievement was significantly associated with patient characteristics, including age, sex, body mass index, lipid-modifying therapy, and CV risk level. CONCLUSIONS:In South Korea, LDL-C goal achievement among patients with very high or high CV risk was suboptimal. Patients who did not achieve the goal showed a higher rate of CV events during the follow-up period than patients who achieved the goal. LDL-C management strategies should be highlighted in dyslipidemia patients who are less likely to achieve the goal, such as female, overweight or obese patients, patients not adherent to statin, or patients with very high or high CV risk.

Dataset Information

Diabetic dyslipidemia and exercise alter the plasma low-density lipoproteome in Yucatan pigs.

Publications

Diabetic dyslipidemia and exercise alter the plasma low-density lipoproteome in Yucatan pigs.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets